Background: Low back pain is among the most common and costly chronic health care conditions. Recent research has highlighted the common occurrence of non-specific low back pain in adolescents, with prevalence estimates similar to adults. While multiple clinical trials have examined the effectiveness of commonly used therapies for the management of low back pain in adults, few trials have addressed the condition in adolescents. The purpose of this paper is to describe the methodology of a randomized clinical trial examining the effectiveness of exercise with and without spinal manipulative therapy for chronic or recurrent low back pain in adolescents. Methods/design: This study is a randomized controlled trial comparing twelve weeks of exercise therapy combined with spinal manipulation to exercise therapy alone. Beginning in March 2010, a total of 184 participants, ages 12 to 18, with chronic or recurrent low back pain are enrolled across two sites. The primary outcome is self-reported low back pain intensity. Other outcomes include disability, quality of life, improvement, satisfaction, activity level, low back strength, endurance, and motion. Qualitative interviews are conducted to evaluate participants’ perceptions of treatment. Discussion: This is the first randomized clinical trial assessing the effectiveness of combining spinal manipulative therapy with exercise for adolescents with low back pain. The results of this study will provide important evidence on the role of these conservative treatments for the management of low back pain in adolescents. Trial registration: (ClinicalTrials.gov NCT01096628).